The broad objective of the proposed research is to identify central neurochemical mechanisms by which severe stress produces persistent changes in the behavioral state of animals. In previous research on this project it has been established that in the rat, various types of acute and chronic stress, such as forced exercise or electric footshock, produce prolonged increases in the turnover of brain catecholamines which are often accompanied by post-stress reductions in gross behavioral activity. There is reason to suspect that prolonged increases in the release of brain amines induced by stress may decrease the sensitivity of central adrenergic receptors, and that this change may result in reduced behavioral activity. One aim of the proposed research, therefore, is to determine the effects of various types of acute and chronic stress on the responsiveness of central catecholamine receptors in rats by measuring (a) the ability of intracerebrally administered norepinephrine (NE) and dopamine (DA) to stimulate motor activity after stress, and (b) the ability of these compounds to stimulate the production of cyclic adenosine monophosphate in vitro in various brain regions of stressed rats. A second aim is to determine if reduced receptor sensitivity after stress is correlated with high levels of catecholamine release as measured by the production of major metabolites of brain NE and DA. A third objective is to determine if central receptors can be made subsensitive by chronic exposure to high levels of catecholamines in the absence of stress by using chronic intraventricular infusions of NE or DA, or by chronic oral administration of amphetamine. BIBLIOGRAPHIC REFERENCES: Stone, E. A., Bonnet, K. A. and Hofer, M. A. Survival and development of maternally deprived rats: role of body temperature. Psychosom. Med. 38:242-249, 1976. Stone, E. A. Central noradrenergic activity and the formation of glycol sulfate metabolites of brain norepinephrine. Life Sci. 1976, In press.